Neoadjuvant Therapy of Pembrolizumab Plus Lenvatinib in Advanced RCC

NCT05485896 | Completed Phase 2 DMC

• 1 other identifier: PELUR
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study to determine the efficacy and safety of Pembrolizumab when given in combination with Lenvatinib as treatment for patients with the advanced kidney cancer. Further evaluate whether the treatment plan is beneficial to the patient's surgery.

Conditions

Renal Cell Carcinoma

Keywords

Pembrolizumab; Lenvatinib; Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Tumor responses

  All patients had imaging (enhanced CT, enhanced MRI or both ) before and after treatment to evaluate radiographic response within the primary tumor and venous tumor thrombus by using RECIST (Response Evaluation Criteria in Solid Tumors)

  Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).

• Adverse events

  Adverse events were monitored throughout treatment until 30 days after surgery and were evaluated according to Common Terminology Criteria for Adverse Events (version 5.0).

  Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).

Secondary Outcomes (2)

• Tumor viability assessment

  Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).

• Progression free survival

  Every 12 weeks until 12 months after surgery

Other Outcomes (1)

• Rate of responser with predictive biomarker positive

  Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).

Study Arms (1)

Advanced RCC (Locally advanced, regional LN invaded, or M1-NED)

EXPERIMENTAL

Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles in the preoperation. In addition, 17 cycles' Pembrolizumab were needed for patients with high risk of recurrence (tumor stage 2 with nuclear grade IV or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph-node metastasis, or stage M1 with no evidence of disease residual).

Drug: Pembrolizumab plus Lenvatinib

Interventions

Pembrolizumab plus Lenvatinib DRUG

Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles in the preoperation. Additional 17 cycles of Pembrolizumab were needed for patients with high risk of recurrence (tumor stage 2 with nuclear grade IV or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph-node metastasis, or stage M1 with no evidence of disease residual).

Advanced RCC (Locally advanced, regional LN invaded, or M1-NED)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent;
• Age ≥ 18 years and age ≤75years;
• Patients with pathologically and radiographically confirmed clear cell renal cell carcinoma with clinical staging: cTanyN1Many, cTanyNanyM1, cT3-4NanyMany, and all visible lesions could be excised or ablation treated;
• Enhanced imaging evaluation can be performed;
• There are no suspected brain metastases;
• The presence of measurable lesions was assessed according to RECISTv1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1;
• Organ function level must meet the following requirements:
• Hematological indexes: neutrophil count \>= 1.5x10\^9/L, platelet count \>= 100x10\^9/L, hemoglobin \>= 9.0 g/dl (can be maintained by blood transfusion); Liver function: total bilirubin \<=1.5 ULN, alanine aminotransferase and aspartate aminotransferase \<=1.5 ULN;
• Women were required to use an effective contraceptive method for three months after the end of the study, and men were required to consent to use an effective contraceptive method with their spouse during and for three months after the end of the study;
• The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up.

You may not qualify if:

• Prior treatment with radiation, chemotherapy, long-term or high-dose hormone therapy, or immune checkpoint inhibitors;
• Previous or concurrent other malignancy;
• Previous PD-L1 or PD-L1 treatment, or allergy to PD-L1;
• History of primary immunodeficiency;
• Active, known or suspected autoimmune diseases;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• Pregnant or lactating female patients;
• Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions;
• Have a clear history of active tuberculosis;
• Participating in other clinical researchers;
• Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
• Uncontrolled concurrent diseases, including but not limited to:
• HIV infected (HIV antibody positive); Severe infection in active stage or poorly controlled; Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment\]); Patients with active bleeding or new thrombotic disease.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

Changyi Quan

Tianjin, Tianjin Municipality, 300211, China

Location

Related Publications (2)

• Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grunwald V, Hutson TE, Kopyltsov E, Mendez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK; CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021 Apr 8;384(14):1289-1300. doi: 10.1056/NEJMoa2035716. Epub 2021 Feb 13.

  PMID: 33616314 BACKGROUND

• Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T; KEYNOTE-564 Investigators. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021 Aug 19;385(8):683-694. doi: 10.1056/NEJMoa2106391.

  PMID: 34407342 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Changyi Quan, MD

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 3, 2022
• Study Start: July 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: September 2, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

CN (1)